scholarly journals Extracellular vesicles and viruses: Are they close relatives?

2016 ◽  
Vol 113 (33) ◽  
pp. 9155-9161 ◽  
Author(s):  
Esther Nolte-‘t Hoen ◽  
Tom Cremer ◽  
Robert C. Gallo ◽  
Leonid B. Margolis
Keyword(s):  
Viral Infection ◽  
Extracellular Vesicles ◽  
Targeted Drug Delivery ◽  
Genetic Material ◽  
Cell Communication ◽  
Viral Proteins ◽  
Phospholipid Membrane ◽  
Infected Cells ◽  
Close Relatives ◽  
Physical And Chemical

Extracellular vesicles (EVs) released by various cells are small phospholipid membrane-enclosed entities that can carry miRNA. They are now central to research in many fields of biology because they seem to constitute a new system of cell–cell communication. Physical and chemical characteristics of many EVs, as well as their biogenesis pathways, resemble those of retroviruses. Moreover, EVs generated by virus-infected cells can incorporate viral proteins and fragments of viral RNA, being thus indistinguishable from defective (noninfectious) retroviruses. EVs, depending on the proteins and genetic material incorporated in them, play a significant role in viral infection, both facilitating and suppressing it. Deciphering the mechanisms of EV-cell interactions may facilitate the design of EVs that inhibit viral infection and can be used as vehicles for targeted drug delivery.

Microglia extracellular vesicles: focus on molecular composition and biological function

2021 ◽  
Vol 49 (4) ◽  
pp. 1779-1790 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Chiara Giacomelli ◽  
Laura Marchetti ◽  
Claudia Martini
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Biological Effects ◽  
Genetic Material ◽  
Cell Communication ◽  
Molecular Composition ◽  
Cargo Proteins ◽  
A Cell ◽  
The Central Nervous System

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.

scholarly journals Diverse populations of extracellular vesicles with opposite functions during herpes simplex virus 1 infection

2020 ◽  
Author(s):  
Christos Dogrammatzis ◽  
Shadia Saleh ◽  
Clayton Deighan ◽  
Maria Kalamvoki
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Extracellular Vesicles ◽  
Functional Characterization ◽  
Cell Communication ◽  
Antiviral Effect ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Extracellular vesicles (EVs) are released by all types of cells as a means of intercellular communication. Their significance lies in the fact that they can alter recipient cells functions, despite their limited capacity for cargo. We have previously demonstrated that herpes simplex virus 1 (HSV-1) infection influences the cargo and functions of EVs released by infected cells, and that these EVs negatively impact a subsequent HSV-1 infection. In the present study, we have implemented cutting-edge technologies to further characterize EVs released during HSV-1 infection. We identified distinct EV populations that were separable through a gradient approach. One population was positive for the tetraspanin CD63 and was distinct from EVs carrying components of the endosomal sorting complexes required for transport (ESCRT). Nanoparticle tracking analysis (NTA) combined with protein analysis indicated that the production of CD63+ EVs was selectively induced upon HSV-1 infection. The ExoView platform supported these data and suggested that the amount of CD63 per vesicle is higher upon infection. This platform also identified EV populations positive for other tetraspanins, including CD81 and CD9, whose abundance decreased upon HSV-1 infection. The STimulator of INterferon Genes (STING) was found in CD63+ EVs released during HSV-1 infection, while viral components were found in ESCRT+ EVs. Functional characterization of these EVs demonstrated that they have opposite effects on the infection, but the dominant effect was negative. Overall, we have identified the dominant population of EVs, and other EV populations produced during HSV-1 infection, and we have provided information about potential roles. Importance Extracellular vesicles mediate cell-to-cell communication and convey messages important for cell homeostasis. Pathways of EV biogenesis are often hijacked by pathogens to facilitate their dissemination and to establish a favorable microenvironment for the infection. We have previously shown that HSV-1 infection alters the cargo and functions of the released EVs, which negatively impact the infection. We have built upon our previous findings by developing procedures to separate EV populations from HSV-1 infected cells. We identified the major population of EVs released during infection, which carries the DNA sensor STING and has an antiviral effect. We also identified an EV population that carries selected viral proteins and has a pro-viral role. This is the first study to characterize EV populations during infection. These data indicate that the complex interactions between the virus and the host are extended to the extracellular environment and could impact HSV-1 dissemination and persistence in the host.

scholarly journals Extracellular Vesicle-Induced Differentiation of Neural Stem Progenitor Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3691 ◽  
Author(s):  
Eleonora Stronati ◽  
Roberta Conti ◽  
Emanuele Cacci ◽  
Silvia Cardarelli ◽  
Stefano Biagioni ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Progenitor Cells ◽  
Extracellular Vesicles ◽  
Peripheral Nerve Regeneration ◽  
Genetic Material ◽  
Cell Communication ◽  
Synaptic Activity ◽  
Dependent Manner ◽  
Neuronal Marker ◽  
Neural Stem Progenitor Cells

Neural stem progenitor cells (NSPCs) from E13.5 mouse embryos can be maintained in culture under proliferating conditions. Upon growth-factor removal, they may differentiate toward either neuronal or glial phenotypes or both. Exosomes are small extracellular vesicles that are part of the cell secretome; they may contain and deliver both proteins and genetic material and thus play a role in cell–cell communication, guide axonal growth, modulate synaptic activity and regulate peripheral nerve regeneration. In this work, we were interested in determining whether NSPCs and their progeny can produce and secrete extracellular vesicles (EVs) and if their content can affect cell differentiation. Our results indicate that cultured NSPCs produce and secrete EVs both under proliferating conditions and after differentiation. Treatment of proliferating NSPCs with EVs derived from differentiated NSPCs triggers cell differentiation in a dose-dependent manner, as demonstrated by glial- and neuronal-marker expression.

scholarly journals Andes Virus Nucleocapsid Protein Interrupts Protein Kinase R Dimerization To Counteract Host Interference in Viral Protein Synthesis

2014 ◽  
Vol 89 (3) ◽  
pp. 1628-1639 ◽  
Author(s):  
Zekun Wang ◽  
Mohammad A. Mir
Keyword(s):  
Protein Kinase ◽  
Viral Infection ◽  
Virus Replication ◽  
Nucleocapsid Protein ◽  
Viral Proteins ◽  
Antiviral Response ◽  
Interferon Response ◽  
Protein Kinase R ◽  
Andes Virus ◽  
Infected Cells

ABSTRACTPathogenic hantaviruses delay the type I interferon response during early stages of viral infection. However, the robust interferon response and induction of interferon-stimulated genes observed during later stages of hantavirus infection fail to combat the virus replication in infected cells. Protein kinase R (PKR), a classical interferon-stimulated gene product, phosphorylates the eukaryotic translation initiation factor eIF2α and causes translational shutdown to create roadblocks for the synthesis of viral proteins. The PKR-induced translational shutdown helps host cells to establish an antiviral state to interrupt virus replication. However, hantavirus-infected cells do not undergo translational shutdown and fail to establish an antiviral state during the course of viral infection. In this study, we showed for the first time that Andes virus infection induced PKR overexpression. However, the overexpressed PKR was not active due to a significant inhibition of autophosphorylation. Further studies revealed that Andes virus nucleocapsid protein inhibited PKR dimerization, a critical step required for PKR autophosphorylation to attain activity. The studies reported here establish a hantavirus nucleocapsid protein as a new PKR inhibitor. These studies provide mechanistic insights into hantavirus resistance to the host interferon response and solve the puzzle of the lack of translational shutdown observed in hantavirus-infected cells. The sensitivity of hantavirus replication to PKR has likely imposed a selective evolutionary pressure on hantaviruses to evade the PKR antiviral response for survival. We envision that evasion of the PKR antiviral response by NP has likely helped hantaviruses to exist during evolution and to survive in infected hosts with a multifaceted antiviral defense.IMPORTANCEProtein kinase R (PKR), a versatile antiviral host factor, shuts down the translation machinery upon activation in virus-infected cells to create hurdles for the manufacture of viral proteins. The studies reported here reveal that the hantavirus nucleocapsid protein counteracts the PKR antiviral response by inhibiting PKR dimerization, which is required for its activation. We report the discovery of a new PKR inhibitor whose expression in hantavirus-infected cells prevents the PKR-induced host translational shutdown to ensure the continuous synthesis of viral proteins required for efficient virus replication.

scholarly journals Exosomes mediate intercellular transmission of porcine reproductive and respiratory syndrome virus (PRRSV)

2017 ◽  
pp. JVI.01734-17 ◽  
Author(s):  
Ting Wang ◽  
Liurong Fang ◽  
Fuwei Zhao ◽  
Dang Wang ◽  
Shaobo Xiao
Keyword(s):  
Intercellular Communication ◽  
Neutralizing Antibodies ◽  
Cell Communication ◽  
Viral Proteins ◽  
Biologically Active ◽  
Productive Infection ◽  
Respiratory Syndrome Virus ◽  
Alternative Mechanism ◽  
Swine Industry ◽  
Infected Cells

Exosomes are small membrane-enclosed vesicles produced by various cells and actively released into the extracellular space. They participate in intercellular communication and transfer of biologically active proteins, lipids and nucleic acids. Accumulating evidence suggests that exosomes derived from cells infected by some viruses selectively encapsulate viral proteins, genetic materials or even virions to mediate cell-to-cell communication and/or virus transmission. Porcine reproductive and respiratory syndrome virus (PRRSV) is anArterivirusthat has been devastating the global swine industry since the late 1980s. Recent studies have shown that major proteins secreted from PRRSV-infected cells are exosomal proteins, and that the serum-derived exosomes from PRRSV-infected pigs contain viral proteins. However, the role of exosomes in PRRSV infection remains unclear. In this study, purified exosomes isolated from PRRSV-infected cells are shown with reverse transcription-PCR and mass spectrometry to contain viral genomic RNA and partial viral proteins. Furthermore, exosomes from PRRSV-infected cells established productive infection in both PRRSV-susceptible and -nonsusceptible cells. More importantly, exosome-mediated infection is not completely blocked by PRRSV-specific neutralizing antibodies. In summary, this study demonstrated that exosomes can mediate PRRSV transmission and are even resistant to antibody neutralization, identifying a potential immune evasion mechanism utilized by PRRSV.IMPORTANCEExosomes have recently been characterized as bioactive vesicles that function to promote intercellular communication. The exosomes from virally infected cells containing altered composition confers numerous novel functionalities. A study of the secretome of cells infected with PRRSV indicated that the exosomal pathway is strongly activated by PRRSV infection. Here, we demonstrate that PRRSV can utilize host exosomes to infect naïve healthy cells. Furthermore, exosome-mediated viral transmission is largely resistant to PRRSV-specific neutralizing antibodies. Our study provides novel insights into an alternative mechanism of PRRSV transmission that can compromise the host's anti-PRRSV immune response.

scholarly journals The Role of Extracellular Vesicles in Viral Infection and Transmission

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 102 ◽  
Author(s):  
Lorena Urbanelli ◽  
Sandra Buratta ◽  
Brunella Tancini ◽  
Krizia Sagini ◽  
Federica Delo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Extracellular Vesicles ◽  
Secretory Pathway ◽  
Cell Entry ◽  
Host Factors ◽  
Intercellular Signaling ◽  
Viral Pathogens ◽  
Infected Cells

Extracellular vesicles (EVs) have been found to be released by any type of cell and can be retrieved in every circulating body fluid, namely blood (plasma, serum), saliva, milk, and urine. EVs were initially considered a cellular garbage disposal tool, but later it became evident that they are involved in intercellular signaling. There is evidence that viruses can use EV endocytic routes to enter uninfected cells and hijack the EV secretory pathway to exit infected cells, thus illustrating that EVs and viruses share common cell entry and biogenesis mechanisms. Moreover, EVs play a role in immune response against viral pathogens. EVs incorporate and spread both viral and host factors, thereby prompting or inhibiting immune responses towards them via a multiplicity of mechanisms. The involvement of EVs in immune responses, and their potential use as agents modulating viral infection, will be examined. Although further studies are needed, the engineering of EVs could package viral elements or host factors selected for their immunostimulatory properties, to be used as vaccines or tolerogenic tools in autoimmune diseases.

scholarly journals Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged?

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 611 ◽  
Author(s):  
Fabio Seiti Yamada Yoshikawa ◽  
Franciane Mouradian Emidio Teixeira ◽  
Maria Notomi Sato ◽  
Luanda Mara da Silva Oliveira
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Cell Communication ◽  
Donor Cell ◽  
Target Cells ◽  
Immune Recognition ◽  
Messenger Rnas ◽  
Pathological Conditions ◽  
Infected Cells ◽  
Cell Profile

Extracellular vesicles (EVs) are released by various cells and recently have attracted attention because they constitute a refined system of cell–cell communication. EVs deliver a diverse array of biomolecules including messenger RNAs (mRNAs), microRNAs (miRNAs), proteins and lipids, and they can be used as potential biomarkers in normal and pathological conditions. The cargo of EVs is a snapshot of the donor cell profile; thus, in viral infections, EVs produced by infected cells could be a central player in disease pathogenesis. In this context, miRNAs incorporated into EVs can affect the immune recognition of viruses and promote or restrict their replication in target cells. In this review, we provide an updated overview of the roles played by EV-delivered miRNAs in viral infections and discuss the potential consequences for the host response. The full understanding of the functions of EVs and miRNAs can turn into useful biomarkers for infection detection and monitoring and/or uncover potential therapeutic targets.

scholarly journals The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies

2021 ◽  
Vol 22 (8) ◽  
pp. 4166
Author(s):  
Saeideh Maleki ◽  
James Jabalee ◽  
Cathie Garnis
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Targeted Therapies ◽  
Genetic Material ◽  
Cell Communication ◽  
Genetic Alterations ◽  
Damage Repair ◽  
Genetic Mechanisms ◽  
Lipid Bilayer Vesicles

Although advances in targeted therapies have driven great progress in cancer treatment and outcomes, drug resistance remains a major obstacle to improving patient survival. Several mechanisms are involved in developing resistance to both conventional chemotherapy and molecularly targeted therapies, including drug efflux, secondary mutations, compensatory genetic alterations occurring upstream or downstream of a drug target, oncogenic bypass, drug activation and inactivation, and DNA damage repair. Extracellular vesicles (EVs) are membrane-bound lipid bilayer vesicles that are involved in cell–cell communication and regulating biological processes. EVs derived from cancer cells play critical roles in tumor progression, metastasis, and drug resistance by delivering protein and genetic material to cells of the tumor microenvironment. Understanding the biochemical and genetic mechanisms underlying drug resistance will aid in the development of new therapeutic strategies. Herein, we review the role of EVs as mediators of drug resistance in the context of cancer.

scholarly journals Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2393
Author(s):  
Jae Hyun Park ◽  
Yuri Choi ◽  
Chul-Woo Lim ◽  
Ji-Min Park ◽  
Shin-Hye Yu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Potential Candidate ◽  
Small Peptides ◽  
Cytopathic Effects ◽  
Human Genes ◽  
Micro Rnas ◽  
Proinflammatory Responses ◽  
Infected Cells ◽  
Viral Responses

Extracellular vesicles (EVs) are cell-released, nanometer-scaled, membrane-bound materials and contain diverse contents including proteins, small peptides, and nucleic acids. Once released, EVs can alter the microenvironment and regulate a myriad of cellular physiology components, including cell–cell communication, proliferation, differentiation, and immune responses against viral infection. Among the cargoes in the vesicles, small non-coding micro-RNAs (miRNAs) have received attention in that they can regulate the expression of a variety of human genes as well as external viral genes via binding to the complementary mRNAs. In this study, we tested the potential of EVs as therapeutic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. First, we found that the mesenchymal stem-cell-derived EVs (MSC-EVs) enabled the rescue of the cytopathic effect of SARS-CoV-2 virus and the suppression of proinflammatory responses in the infected cells by inhibiting the viral replication. We found that these anti-viral responses were mediated by 17 miRNAs matching the rarely mutated, conserved 3′-untranslated regions (UTR) of the viral genome. The top five miRNAs highly expressed in the MSC-EVs, miR-92a-3p, miR-26a-5p, miR-23a-3p, miR-103a-3p, and miR-181a-5p, were tested. They were bound to the complemented sequence which led to the recovery of the cytopathic effects. These findings suggest that the MSC-EVs are a potential candidate for multiple variants of anti-SARS-CoV-2.

Sign in / Sign up

Export Citation Format

Share Document